The novel arthroscopic subscapular sling procedure grants better stability than an arthroscopic Bankart repair in a cadaveric study.
This novel arthroscopic subscapular sling procedure stabilizes the shoulder using a semitendinosus graft to create a sling around the subscapular tendon, which provides both static and dynamic stability. The aim of the study was to evaluate the biomechanical stability of the subscapular sling procedure in human cadaveric shoulders. The hypothesis was that the sling offers an equal stabilizing effect and range of motion compared to an arthroscopic Bankart repair. Sixteen shoulders were investigated using an industrial robot-based testing platform and four different conditions: the physiologically intact shoulder, after creating a Bankart lesion, after arthroscopic Bankart repair, and finally after applying the subscapular sling procedure using a semitendinosus tendon graft. Joint translation and external rotation were evaluated for each condition. The results show improved stability in the shoulders with the subscapular sling. The robot testing revealed a significant reduction in translation in anterior and anterior-inferior directions compared to the arthroscopic Bankart repair. None of the shoulders were dislocated by forced manual abduction and external rotation. No difficulties were encountered in performing the arthroscopic subscapular sling procedure. Thorough postoperative anatomical dissection showed no alterations to structures at risk. The biomechanical results show increased stability with the use of the subscapular sling method.


Simple and efficient estimation of photovoltaic cells and modules parameters using approximation and correction technique.
The behavior of solar cells and modules under various operational conditions can be determined effectively when their intrinsic parameters are accurately estimated and used to simulate the current-voltage (I-V) characteristics. This work proposed a new computational approach based on approximation and correction technique (ACT) for simple and efficient extraction of solar cells and modules parameters from the single-diode model. In this technique, an approximated value of series resistance (Rs) was first derived and used to determine the initial value of parallel resistance (Rp). Later, the final corrected values of Rs and Rp were obtained by resubstituting their approximated values in a five-loop iteration using the manipulated equations. For rapid evaluation and validation of the proposed technique, a software application was also created using MATLAB program. The correctness and robustness of the proposed technique was validated on five types of solar cells and modules operated at varied temperatures and irradiances. The lowest RMSE value was achieved for RTC France (7.78937E-4) and PVM 752 GaAs (2.10497E-4) solar cell. The legitimacy of ACT extracted parameters was established using a simple yet competitive implementation approach wherein the performance of the developed technique was compared with several state-of-the-art methods recently reported in the literature.


The Glu²¹⁶/Ser²¹⁸ pocket is a major determinant of spermine oxidase substrate specificity.
SMO (spermine oxidase) and APAO (acetylpolyamine oxidase) are flavoenzymes that play a critical role in the catabolism of polyamines. Polyamines are basic regulators of cell growth and proliferation and their homoeostasis is crucial for cell life since dysregulation of polyamine metabolism has been linked with cancer. In vertebrates SMO specifically catalyses the oxidation of spermine, whereas APAO displays a wider specificity, being able to oxidize both N¹-acetylspermine and N¹-acetylspermidine, but not spermine. The molecular bases of the different substrate specificity of these two enzymes have remained so far elusive. However, previous molecular modelling, site-directed mutagenesis and biochemical characterization studies of the SMO enzyme-substrate complex have identified Glu²¹⁶-Ser²¹⁸ as a putative active site hot spot responsible for SMO substrate specificity. On the basis of these analyses, the SMO double mutants E216L/S218A and E216T/S218A have been produced and characterized by CD spectroscopy and steady-state and rapid kinetics experiments. The results obtained demonstrate that mutation E216L/S218A endows SMO with N¹-acetylspermine oxidase activity, uncovering one of the structural determinants that confer the exquisite and exclusive substrate specificity of SMO for spermine. These results provide the theoretical bases for the design of specific inhibitors either for SMO or APAO.


Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP.
The first third (ca. 1200 bp) of exon 1 of the nuclear gene encoding the interstitial retinoid-binding protein (IRBP) has been sequenced for 12 representative primates belonging to Lemuriformes, Lorisiformes, Tarsiiformes, Platyrrhini, and Catarrhini, and combined with available data (13 other primates, 11 nonprimate placentals, and 2 marsupials). Phylogenetic analyses using maximum likelihood on nucleotides and amino acids robustly support the monophyly of primates, Strepsirrhini, Lemuriformes, Lorisiformes, Anthropoidea, Catarrhini, and Platyrrhini. It is interesting to note that 1) Tarsiidae grouped with Anthropoidea, and the support for this node depends on the molecular characters considered; 2) Cheirogaleidae grouped within Lemuriformes; and 3) Daubentonia was the sister group of all other Lemuriformes. Study of the IRBP evolutionary rate shows a high heterogeneity within placentals and also within primates. Maximum likelihood local molecular clocks were assigned to three clades displaying significantly contrasted evolutionary rates. Paenungulata were shown to evolve 2.5-3 times faster than Perissodactyla and Lemuriformes. Six independent calibration points were used to estimate splitting ages of the main primate clades, and their compatibility was evaluated. Divergence ages were obtained for the following crown groups: 13.8-14.2 MY for Lorisiformes, 26.5-27.2 MY for Lemuroidea, 39.6-40.7 MY for Lemuriformes, 45.4-46.7 MY for Strepsirrhini, and 56.7-58.4 MY for Haplorrhini. The incompatibility between some paleontological and molecular estimates may reflect the incompleteness of the placental fossil record, and/or indicate that the variable IRBP evolutionary rates are not fully accommodated by local molecular clocks.


Diagnostic accuracy of transabdominal sonography in the evaluation of pelvic mass of gynecological origin.
A study of 97 cases having clinical manifestations of pelvic mass in female was carried out in the department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University with the cooperation of the department of Obstetrics and Gynecology. This study was designed to determine accuracy of transabdominal sonography in the diagnosis of pelvic mass in female. The findings of transabdominal sonography were compared with histopathological examination. Transabdominal sonography had 87.6% accuracy, but only 3.1% false positive and 9.3% false negative rates. It can be concluded that ultrasonographic findings of different pelvic masses are highly dependable, can be used for preoperative decision making.


Perinatal outcome in renal allograft recipients: prognostic significance of hypertension and renal function before and during pregnancy.
With more renal allograft recipients becoming pregnant, it is important to refine existing pre-pregnancy assessment criteria and to identify other factors influencing perinatal outcome. We analyzed gestational renal response and acute or chronic hypertension in relation to perinatal outcome for 22 pregnancies that continued beyond 28 weeks' gestation in 17 allograft recipients (mean age 27 years, range 20-40) transplanted between 1967-1987. Before pregnancy, all had plasma creatinine of 1.62 mg/dL or less and 24-hour creatinine clearance of 39 mL/minute or greater. Six pregnancies were to four women on antihypertensive therapy. Mean arterial pressure (MAP), antihypertensive therapy, plasma creatinine, and 24-hour creatinine clearance were recorded before and during pregnancy. Perinatal outcome was adverse in ten pregnancies: five stillbirths, four growth-retarded infants, and one neonatal death, whereas 12 pregnancies had satisfactory perinatal outcome. Early-pregnancy increments and late-pregnancy decrements in renal function were identical in both groups. Mean arterial pressure was significantly higher at 16-28 weeks in women having adverse outcomes. Hypertension (MAP above 107 mmHg) occurred in 16 pregnancies (73%); it appeared before 28 weeks in seven and was invariably associated with adverse outcome. Hypertension appeared after 28 weeks in nine women and was associated with adverse outcome in only two cases. Five of six pregnancies in women who were on pre-pregnancy antihypertensive therapy ended in adverse outcome. It can be concluded that renal function was identical in pregnancies having adverse or satisfactory perinatal outcome, whereas hypertension before or during early pregnancy, albeit apparently satisfactorily controlled, appeared to be associated with adverse perinatal outcome.


Activation of mammalian ribosomal gene transcription requires phosphorylation of the nucleolar transcription factor UBF.
The nucleolar factor UBF is phosphorylated by casein kinase II (CKII) at serine residues within the C-terminal acidic domain which is required for transcription activation. To investigate the biological significance of UBF modification, we have compared the trans-activating properties of cellular UBF and recombinant UBF expressed in Escherichia coli. Using a variety of assays we demonstrate that unphosphorylated UBF is transcriptionally inactive and has to be phosphorylated at multiple sites to stimulate transcription. Examination of cDNA mutants in which the serine residues within the C-terminal domain were altered by site-directed mutagenesis demonstrates that CKII-mediated phosphorylations of UBF contribute to, but are not sufficient for, transcriptional activation. Besides CKII, other cellular protein kinases phosphorylate UBF at distinct sites in a growth-dependent manner. The marked differences in the tryptic peptide maps of UBF from growing and serum-starved cells suggest that alterations in the degree of UBF phosphorylation may modulate rRNA synthetic activity in response to extracellular signals.


Risk factors for subtrochanteric and diaphyseal fractures: the study of osteoporotic fractures.
Patients on long-term bisphosphonate therapy may have an increased incidence of low-energy subtrochanteric and diaphyseal (SD) femoral fractures. However, the incidence and risk factors associated with these fractures have not been well defined. The objective of the study was to determine the incidence of and risk factors for low-energy SD fractures in the Study of Osteoporotic Fractures (SOF). Low-energy SD fractures were identified from a review of radiographic reports obtained between 1986 and 2010 in women in the SOF. Among the SD fractures, pathological, periprosthetic, and traumatic fractures were excluded. We assessed risk factors for SD fractures as well as risk factors for femoral neck (FN) and intertrochanteric (IT) hip fractures using both age-adjusted and multivariate time-dependent proportional hazards models. During this follow-up, only a small minority had ever used bisphosphonates. Forty-five women sustained low-energy subtrochanteric/diaphyseal femoral fractures over a total follow-up of 140 000 person-years. The incidence of SD fracture was 3.2 per 10 000 person-years compared with a total hip fracture incidence of 110 per 10 000 person-years. A total of about 12% of women reported bisphosphonate use at 1 or more visits. In multivariate analyses, age, total hip bone mineral density (BMD), bisphosphonate use, and history of diabetes emerged as independent risk factors for SD fractures. Risk factors for FN and IT fractures included age, BMD, and history of falls or prior fractures. Bisphosphonate use was protective against FN fractures, whereas there was an increased risk of SD fractures (hazard ratio 2.58, P = .049) with bisphosphonate use after adjustment for other risk factors for fracture. In SOF, low-energy SD fractures were rare occurrences, far outnumbered by FN and IT fractures. Typical risk factors were associated with FN and IT fractures, whereas only age, total hip BMD, and history of diabetes were independent risk factors for SD fractures. In addition, bisphosphonate use was a marginally significantly predictor although the SOF study has limited ability to assess this association.


Posterior labral injury in contact athletes.
Nine athletes (seven football offensive linemen, one defensive lineman, and one lacrosse player) were found at arthroscopy to have posterior labral detachment from the glenoid. In our series, this lesion is specific to contact athletes who engage their opponents with arms in front of the body. All patients had pain with bench pressing and while participating in their sport, diminishing their ability to play effectively. Conservative measures were ineffective in relieving their symptoms. Examination under anesthesia revealed symmetric glenohumeral translation bilaterally, without evidence of posterior instability. Treatment consisted of glenoid rim abradement and posterior labral repair with a bioabsorbable tack. All patients returned to complete at least one full season of contact sports and weightlifting without pain (minimum follow-up, > or = 2 years). Although many injuries leading to subluxation of the glenohumeral joint occur when an unanticipated force is applied, contact athletes ready their shoulder muscles in anticipation of impact with opponents. This leads to a compressive force at the glenohumeral joint. We hypothesize that, in combination with a posteriorly directed force at impact, the resultant vector is a shearing force to the posterior labrum and articular surface. Repeated exposure leads to posterior labral detachment without capsular injury. Posterior labral reattachment provides consistently good results, allowing the athlete to return to competition.


Evaluation of lateral flow devices for postmortem rabies diagnosis in animals in the Philippines: a multicenter study.
Expansion of the use of lateral flow devices (LFD) for animal rabies diagnosis can help mitigate the widespread underreporting of rabies. However, this has been hindered by the limited number and small sample size of previous studies. To overcome this limitation, we conducted a multicenter study with a larger sample size to assess the diagnostic accuracy of the ADTEC LFD for postmortem rabies diagnosis in animals. Thirteen governmental animal diagnostic laboratories in the Philippines were involved in this study, and 791 animals suspected of having rabies were tested using both the direct fluorescence antibody test (DFAT) and ADTEC LFD between August 2021 and October 2022. The LFD demonstrated a sensitivity of 96.3% [95% confidence interval (CI): 94.1%-97.9%] and a specificity of 99.7% (95% CI: 98.4%-100%). Notably, false-negative results were more likely to occur in laboratories with lower annual processing volumes of rabies samples in the previous years (adjusted odds ratio 4.97, 95% CI: 1.49-16.53). In this multicenter study, the high sensitivity and specificity of the LFD for the diagnosis of animal rabies, compared to that of the DFAT, was demonstrated, yet concerns regarding false-negative results remain. In areas with limited experience in processing rabies samples, it is essential to provide comprehensive training and careful attention during implementation.


Perspective taking as virtual navigation? Perceptual simulation of what others see reflects their location in space but not their gaze.
Other peoples' (imagined) visual perspectives are represented perceptually in a similar way to our own, and can drive bottom-up processes in the same way as own perceptual input (Ward, Ganis, & Bach, 2019). Here we test directly whether visual perspective taking is driven by where another person is looking, or whether these perceptual simulations represent their position in space more generally. Across two experiments, we asked participants to identify whether alphanumeric characters, presented at one of eight possible orientations away from upright, were presented normally, or in their mirror-inverted form (e.g. "R" vs. "Я"). In some scenes, a person would appear sitting to the left or the right of the participant. We manipulated either between-trials (Experiment 1) or between-subjects (Experiment 2), the gaze-direction of the inserted person, such that they either (1) looked towards the to-be-judged item, (2) averted their gaze away from the participant, or (3) gazed out towards the participant (Exp. 2 only). In the absence of another person, we replicated the well-established mental rotation effect, where recognition of items becomes slower the more items are oriented away from upright (e.g. Shepard and Meltzer, 1971). Crucially, in both experiments and in all conditions, this response pattern changed when another person was inserted into the scene. People spontaneously took the perspective of the other person and made faster judgements about the presented items in their presence if the characters were oriented towards upright to them. The gaze direction of this other person did not influence these effects. We propose that visual perspective taking is therefore a general spatial-navigational ability, allowing us to calculate more easily how a scene would (in principle) look from another position in space, and that such calculations reflect the spatial location of another person, but not their gaze.


Quality of Dietary Fat Intake and Body Weight and Obesity in a Mediterranean Population: Secondary Analyses within the PREDIMED Trial.
A moderately high-fat Mediterranean diet does not promote weight gain. This study aimed to investigate the association between dietary intake of specific types of fat and obesity and body weight. A prospective cohort study was performed using data of 6942 participants in the PREDIMED trial, with yearly repeated validated food-frequency questionnaires, and anthropometric outcomes (median follow-up: 4.8 years). The effects of replacing dietary fat subtypes for one another, proteins or carbohydrates were estimated using generalized estimating equations substitution models. Replacement of 5% energy from saturated fatty acids (SFA) with monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA) resulted in weight changes of -0.38 kg (95% Confidece Iinterval (CI): -0.69, -0.07), and -0.51 kg (95% CI: -0.81, -0.20), respectively. Replacing proteins with MUFA or PUFA decreased the odds of becoming obese. Estimates for the daily substitution of one portion of red meat with white meat, oily fish or white fish showed weight changes up to -0.87 kg. Increasing the intake of unsaturated fatty acids at the expense of SFA, proteins, and carbohydrates showed beneficial effects on body weight and obesity. It may therefore be desirable to encourage high-quality fat diets like the Mediterranean diet instead of restricting total fat intake.


Using geospatial social media data for infectious disease studies: a systematic review.
Geospatial social media (GSM) data has been increasingly used in public health due to its rich, timely, and accessible spatial information, particularly in infectious disease research. This review synthesized 86 research articles that use GSM data in infectious diseases published between December 2013 and March 2022. These articles cover 12 infectious disease types ranging from respiratory infectious diseases to sexually transmitted diseases with spatial levels varying from the neighborhood, county, state, and country. We categorized these studies into three major infectious disease research domains: surveillance, explanation, and prediction. With the assistance of advanced statistical and spatial methods, GSM data has been widely and deeply applied to these domains, particularly in surveillance and explanation domains. We further identified four knowledge gaps in terms of contextual information use, application scopes, spatiotemporal dimension, and data limitations and proposed innovation opportunities for future research. Our findings will contribute to a better understanding of using GSM data in infectious diseases studies and provide insights into strategies for using GSM data more effectively in future research.


A Noise-Filtered Under-Sampling Scheme for Imbalanced Classification.
Under-sampling is a popular data preprocessing method in dealing with class imbalance problems, with the purposes of balancing datasets to achieve a high classification rate and avoiding the bias toward majority class examples. It always uses full minority data in a training dataset. However, some noisy minority examples may reduce the performance of classifiers. In this paper, a new under-sampling scheme is proposed by incorporating a noise filter before executing resampling. In order to verify the efficiency, this scheme is implemented based on four popular under-sampling methods, i.e., Undersampling + Adaboost, RUSBoost, UnderBagging, and EasyEnsemble through benchmarks and significance analysis. Furthermore, this paper also summarizes the relationship between algorithm performance and imbalanced ratio. Experimental results indicate that the proposed scheme can improve the original undersampling-based methods with significance in terms of three popular metrics for imbalanced classification, i.e., the area under the curve, -measure, and -mean.


Drugs, discrimination and disability.
Whether addiction to prohibited drugs should be classified as a disability for the purposes of disability discrimination is a controversial question in Australia. The leading Australian case of Marsden v Human Rights Equal Opportunity Commission & Coffs Harbour & District Ex-Servicemen & Women's Memorial Club Ltd (HREOC, No H98/51, 30 August 1999); [2000] FCA 1619 concerned a disability discrimination complaint brought by Mr Marsden as a result of his treatment by the club. The case was brought as a public interest test case by the New South Wales Legal Aid Commission. Mr Marsden was on a methadone program at the time. The reasoning of the decision at the Federal Court opened the way for a finding that dependence on illegal drugs constituted a disability under disability discrimination legislation. The media reaction to the court's decision led to State and federal governments proposing legislation limiting legal protection from discrimination for people addicted to illegal drugs on the basis of their drug use. While the proposed federal legislation lapsed after objections from a coalition of medical, legal and other advocacy groups, the New South Wales legislation still provides that, in employment matters, it is not unlawful to discriminate against a person on the ground of disability if the disability relates to the person's addiction to a prohibited drug and the person is actually addicted to a prohibited drug at the time of the discrimination. The article details the sequence of events in the Marsden case, reflects on the role of public interest litigation in achieving social justice outcomes and suggests that Australia's recent ratification of the Convention on the Rights of Persons with Disabilities on 17 July 2008 should encourage legislators to review legislation which may have a discriminatory effect on people suffering from addictions.


Regenerative endodontics: A way forward.
Immature teeth are susceptible to infections due to trauma, anatomic anomalies, and caries. Traditional endodontic therapies for immature teeth, such as apexification procedures, promote resolution of the disease and prevent future infections. However, these procedures fail to promote continued root development, leaving teeth susceptible to fractures. Regenerative endodontic procedures (REPs) have evolved in the past decade, being incorporated into endodontic practice and becoming a viable treatment alternative for immature teeth. The authors have summarized the status of regenerative endodontics on the basis of the available published studies and provide insight into the different levels of clinical outcomes expected from these procedures. Substantial advances in regenerative endodontics are allowing a better understanding of a multitude of factors that govern stem cell-mediated regeneration and repair of the damaged pulp-dentin complex. REPs promote healing of apical periodontitis, continued radiographic root development, and, in certain cases, vitality responses. Despite the clinical success of these procedures, they appear to promote a guided endodontic repair process rather than a true regeneration of physiological-like tissue. Immature teeth with pulpal necrosis with otherwise poor prognosis can be treated with REPs. These procedures do not preclude the possibility of apexification procedures if attempts are unsuccessful. Therefore, REPs may be considered first treatment options for immature teeth with pulpal necrosis.


Comorbid mental disorders: implications for treatment and sample selection.
Disorders from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) were assessed in a birth cohort of 961 young adults. Comorbid cases exceeded single-disordered cases in chronic history of mental illness, use of treatments, physical health problems, functional interference in daily life, and impaired adaptation across domains such as work, education, health, and social-support networks. Single-disorder cases were also more impaired than nondisordered cases, but comorbid cases were the most severely impaired. Our findings suggest that (a) samples that underrepresent comorbidity (pure single-disorder cases or student samples) will underestimate effect sizes for relations between a disorder and its correlates, whereas samples that overrepresent comorbidity (clinical or adjudicated samples) will overestimate effect sizes, (b) comorbidity is accompanied by complications that challenge treatment planning, compliance, and coordination of service delivery, and (c) comorbidity is associated with physical, educational, and economic problems that make it a broad societal concern.


Effect of anticipation on knee kinematics during a stop-jump task.
Knee stability during a functional assessment of the stop-jump task is a key factor to determine if an athlete is adequately rehabilitated after knee ligamentous injury. This study aimed to investigate knee stability due to the effect of anticipation on landing maneuvers during planned and unplanned stop-jump tasks. Knee kinematics of ten healthy male participants were collected using an optical motion analysis system during stop-jump tasks. Stop jumps were performed in four different landing positions either in planned movement or in an unplanned movement on a signal triggered as participants passed through a photocell gate. Kinematic data at the time of foot strike at landing in the stop-jump considered for investigating the anticipation effect during the stop-jump tasks. Two-way multivariate analysis of variance (MANOVA) with repeated measures and stratified paired t-tests were conducted to compare the knee kinematics data between planned and unplanned tasks. Statistical significance was set at the p<0.05 level. External rotational angle showed a significant decrease in unplanned stop-jump tasks during forward (p<0.05) and right (p<0.05) jumps when compared to that of planned tasks. Flexion angle and abduction angle during forward, vertical and right jumps were significantly decreased in the unplanned tasks. Anticipation significantly influenced the landing maneuvers of stop-jump task. The results indicated that both planned and unplanned stop-jump tasks should be considered when monitoring the rehabilitation progress after a ligamentous injury.


Thrombocytopenic purpura as adverse reaction to recombinant hepatitis B vaccine.
Three cases of immune thrombocytopenic purpura after the first dose of recombinant hepatitis B vaccine occurred in infants under 6 months of age. Other possible causes of this condition were excluded. Antiplatelet antibodies were present. A defect in platelet production was excluded in two children. Corticosteroid treatment was effective. Subsequent administration of other vaccines (against polio, diphtheria, and tetanus) did not cause relapse of thrombocytopenia.


GH therapy in transition age: state of the art and future perspectives.
Growth hormone (GH) has been recently approved by the Italian Health Authorities for use in transition patients with childhood onset-growth hormone deficiency (CO-GHD). GH in addition to promote linear growth influences several key metabolic processes. In particular, in the transition period, from late adolescent to early adulthood, GH plays an important role in the achievement of a complete somatic development including body composition, muscle mass maturation, full skeletal mineralization and reproductive maturation, as well as in the prevention of metabolic and cardiovascular risk. Therefore, GH replacement should be restarted if a GH stimulation test at the re-evaluation fulfills established criteria. Endocrinologists experienced in the care of GHD adolescent patients held a workshop in Rome, Italy in July 2012 to review in detail the literature data and compare experiences of five Italian endocrinological centers on the negative consequences of interrupting GH treatment and the positive effects of continued GH replacement on intermediary metabolism, heart, muscle, pubertal development, and bone. The aim of the meeting was to delineate the state of the art on GH therapy in transition age and provide suggestions to pediatric and adult endocrinologists for a smooth transition care.


S-Nitrosothiols: a class of nitric oxide-donor drugs.
Nitric oxide (NO) was originally described as the principal endothelium-derived relaxing factor, but it is now known to subserve a variety of functions throughout the body, both physiological and pathophysiological. NO-donor drugs decompose in the body, by a variety of mechanisms, to generate NO. Such drugs have been used for many years in cardiovascular therapeutics, in particular the organic nitrates for the prevention and treatment of angina pectoris and sodium nitroprusside for the treatment of hypertensive emergencies. However, patients taking long-term nitrates often develop tolerance, and prolonged nitroprusside administration can give rise to cyanide accumulation in the body. Newer NO-donor drugs, in particular the S-nitrosothiols, offer advantages over the existing drugs, since they do not share these drawbacks, and initial small clinical studies suggest that they may be of benefit in a variety of cardiovascular disorders. Here we briefly review the chemistry and physiology of NO, and discuss the chemistry and clinical possibilities of the S-nitrosothiols.


Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition.
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate. Steatohepatitis and fibrosis were induced by feeding Atg7 wild-type, haploinsufficient, and knockout mice a methionine- and choline-deficient diet with ezetimibe (10 mg/kg) for 4 wk. Human livers with steatosis or NASH presented impaired autophagy with decreased nuclear TFEB and increased SQSTM1, MAP1LC3-II, and NLRP3 expression. Ezetimibe increased autophagy flux and concomitantly ameliorated lipid accumulation and apoptosis in palmitate-exposed hepatocytes. Ezetimibe induced AMPK phosphorylation and subsequent TFEB nuclear translocation, related to MAPK/ERK. In macrophages, ezetimibe blocked the NLRP3 inflammasome-IL1B pathway in an autophagy-dependent manner and modulated hepatocyte-macrophage interaction via extracellular vesicles. Ezetimibe attenuated lipid accumulation, inflammation, and fibrosis in liver-specific Atg7 wild-type and haploinsufficient mice, but not in knockout mice. Ezetimibe ameliorates steatohepatitis by autophagy induction through AMPK activation and TFEB nuclear translocation, related to an independent MTOR ameliorative effect and the MAPK/ERK pathway. Ezetimibe dampens NLRP3 inflammasome activation in macrophages by modulating autophagy and a hepatocyte-driven exosome pathway.


Veterans individual placement and support towards advancing recovery: Methods and baseline clinical characteristics of a multisite study.
This article describes the methodology and the baseline characteristics of veterans with posttraumatic stress disorder (PTSD) enrolled in a multisite trial comparing supported employment individual placement and support (IPS) to a stepwise vocational transitional work program (TWP). The Veterans Affairs Cooperative Studies Program randomized 541 veterans with PTSD across 12 Veterans Affairs Medical Centers to either IPS or TWP. Demographic and clinical characteristics were evaluated at baseline. Participants averaged 42 (SD ± 11) years of age and had PTSD for 13 (SD ± 11) years. The group was comprised of 18% female, 42% African Americans, and 16% Latino participants. Approximately 60% of participants served in the military since 2001, 89% were receiving or applying for service-connected disability, 60% had PTSD from nonsexual combat-related trauma, and 17% had PTSD from military sexual trauma. One third had not held a competitive job in the past 3 years; the average length of unemployment was 2.8 (SD ± 4) years. Unique study features included the focus on veterans with PTSD, a comparison of a promising practice with a usual-care practice, and the outcome criterion of achieving steady competitive employment. Conclusions and Implication for Practice: This study is the first large-scale randomized trial of IPS in a PTSD population. These baseline findings illustrate the characteristics of the study sample, which are representative of a veteran population in need of vocational rehabilitation services and can be used to help guide the implementation of tailored veteran-centered programs. (PsycINFO Database Record


Continuing Professional Development through the lens of complexity science: Becoming agents of change in the healthcare system.
This article was migrated. The article was marked as recommended. Healthcare improvement initiatives have not led to expected changes in patient population outcomes over the last decade. This can, in part, be explained by overly reductionist approaches in medical practice and education. This article describes some insights and experiences using a Complex Adaptive Systems approach in the conceptualisation of an in-service training program and reflections on elements that may lead to enhanced practice behaviours and system improvements.


[Fiberoptic endoscopic swallowing disorders in chronic encephalopathy]
OBJECTIVE: To evaluate the results of fiberoptic endoscopic examination of swallowing safety in children with cerebral encephalopathy in order to identify patients with oropharyngeal dysphagia. METHODS: 68 children from the Association for the Care of Disabled Children (Associação de Assistência à Criança Deficiente -AACD), São Paulo, were submitted to fiberoptic endoscopic examination of swallowing safety from March 1999 to March 2000. RESULTS: We observed premature spillage (53%), penetration in a pureed consistency (5.9%), penetration in a liquid consistency (4.4%), tracheal aspiration in a pureed consistency (14.7%), tracheal aspiration in a liquid consistency (32.3%), residue (7.4%), cough effectiveness (44.1%). CONCLUSIONS: Children showed a high incidence of pharyngeal swallowing disorders. Tracheal aspiration was the most important disorder because it is related with high morbidity in children with cerebral encephalopathy. The texture and consistency of the patientacute;s diet may be modified to decrease the risk of aspiration and improve swallowing examination.


Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: roles for cortactin and myosin light chain kinase.
We recently reported the critical importance of Rac GTPase-dependent cortical actin rearrangement in the augmentation of pulmonary endothelial cell (EC) barrier function by sphingosine 1-phosphate (S1P). We now describe functional roles for the actin-binding proteins cortactin and EC myosin light chain kinase (MLCK) in mediating this response. Antisense down-regulation of cortactin protein expression significantly inhibits S1P-induced barrier enhancement in cultured human pulmonary artery EC as measured by transendothelial electrical resistance (TER). Immunofluorescence studies reveal rapid, Rac-dependent translocation of cortactin to the expanded cortical actin band following S1P challenge, where colocalization with EC MLCK occurs within 5 min. Adenoviral overexpression of a Rac dominant negative mutant attenuates TER elevation by S1P. S1P also induces a rapid increase in cortactin tyrosine phosphorylation (within 30 s) critical to subsequent barrier enhancement, since EC transfected with a tyrosine-deficient mutant cortactin exhibit a blunted TER response. Direct binding of EC MLCK to the cortactin Src homology 3 domain appears essential to S1P barrier regulation, since cortactin blocking peptide inhibits both S1P-induced MLC phosphorylation and peak S1P-induced TER values. These data support novel roles for the cytoskeletal proteins cortactin and EC MLCK in mediating lung vascular barrier augmentation evoked by S1P.


Institutional Experience of Treatment and Outcomes for Cutaneous Periauricular Squamous Cell Carcinoma.
To report our institutional experience, management, and outcomes of cutaneous periauricular squamous cell carcinoma (SCC). Retrospective chart review. Tertiary academic center. Patients undergoing treatment of cutaneous periauricular SCC from 2000 to 2016. A total of 112 patients had a median follow-up of 24.5 months, a mean ± SD age of 75.7 ± 10.6 years, and a strong male predominance (93.8%). Site distribution shows 87 (77.7%) auricular, 26 (23.2%) preauricular, and 10 (8.8%) postauricular lesions. Of auricular lesions, tumors involved the tragus (n = 3, 3.4%), helix/antihelix (n = 47, 54.0%), conchal bowl (n = 31, 35.6%), external auditory canal (n = 18, 16.1%), and lobule (n = 3, 3.4%). Most patients presented at stage I (52.7%) versus stages II (28.6%), III (6.3%), and IV (12.5%). Patients were largely treated surgically with primary tumor resection ranging from wide local excision to lateral temporal bone resection (± parotidectomy and neck dissection), with 17.0% and 5.4% receiving adjuvant radiation and chemoradiation, respectively. Metastatic spread was seen to the parotid (25.9%) and neck (26.8%), with most common cervical spread to level II. Overall survival, disease-specific survival, and disease-free survival at 3 years were 62%, 89%, and 56%, respectively. Nodal disease was associated with worse disease-specific survival (P < .001) and disease-free survival (P = .042). Pre- and postauricular sites were associated with worse overall survival (P = .007) relative to auricular sites. Among cutaneous SCC, periauricular subsites pose treatment challenges related to surrounding anatomy and represent a unique tumor population. The reported propensity toward recurrence and patterns of metastasis may better guide treatment of aggressive tumors to include regional nodal dissection.


Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation.
Several human and experimental autoimmune diseases, including the current model for multiple sclerosis (MS), ie relapsing experimental autoimmune encephalomyelitis (R-EAE), have been reported to respond with complete remission to lympho- and myeloablation and rescue with transplantation of bone marrow (BMT) from healthy donors. Since treatment with autologous BM was as effective in our arthritis model as treatment with allogeneic BM from healthy rats, and in view of the much lower risk of autologous BMT in clinical practice, we have investigated treatment of R-EAE with pseudo-autologous (PSA) BM. PSABM is harvested from animals in the same active stage of R-EAE as the syngeneic recipients which are to be treated. Our results show that PSABM is as effective as syngeneic BM, except for a higher incidence of artificially induced relapses. We also demonstrated that lymphocytes present in the autologous BM graft may contribute to the occurrence of relapses post-transplantation. The implications of our results for a possible clinical application in the treatment of MS patients are discussed. If such treatment is envisaged, the use of T cell-depleted autografts seems mandatory, particularly as human BM contains 10 times more lymphocytes than rat BM.


The impact of estimation methods for alcohol-attributable mortality on long-term trends for the general population and by educational level in Finland and Italy (Turin).
This paper assesses the impact of estimation methods for general and education-specific trends in alcohol-attributable mortality (AAM), and develops an alternative method that can be used when the data available for study is limited. We calculated yearly adult (30+) age-standardised and age-specific AAM rates by sex for the general population and by educational level (low, middle, high) in Finland and Turin (Italy) from 1972 to 2017. Furthermore the slope index of inequality and relative inequality index were computed by country and sex. We compared trends, levels, age distributions, and educational inequalities in AAM according to three existing estimation methods: (1) Underlying COD (UCOD), (2) Multiple COD (MCOD) method, and (3) the population attributable fractions (PAF)-method. An alternative method is developed based on the pros and cons of these methods and the outcomes of the comparison. The UCOD and MCOD approaches revealed mainly increasing trends in AAM compared to the declining trends according to the PAF approach. These differences are more pronounced when examining AAM trends by educational groups, particularly for Finnish men. Until age 65, age patterns are similar for all methods, and levels nearly identical for MCOD and PAF in Finland. Our novel method assumes a similar trend and age pattern as observed in UCOD, but adjusts its level upwards so that it matches the level of the PAF approach for ages 30-64. Our new method yields levels in-between UCOD and PAF for Turin (Italy), and resembles the MCOD rates in Finland for females. Relative inequalities deviate for the PAF-method (lower levels) compared to other methods, whereas absolute inequalities are generally lower for UCOD than all three methods that combine wholly and partly AAM. The choice of method to estimate AAM affects not only levels, but also general and education-specific trends and inequalities. Our newly developed method constitutes a better alternative for multiple-country studies by educational level than the currently used UCOD-method when the data available for study is limited to underlying causes of death.


[Effect of N-methyl-D-aspartate on the spontaneous activity generated by isolated spinal cord of 16 to 20-day-old chick embryos].
Bath-application of N-methyl-D-aspartate (NMDA) and antagonist of NMDA-receptors 2-amino-5-phosphonovaleric acid (2-APV) has been studied from the standpoint of its effect on the spontaneous activity in dorsal and ventral roots (DR and VR, respectively) generated by isolated spinal cord of 16-20-day-old chick embryo. Spontaneous activity consisted of synchronous oscillations of electrotonic potentials in DR and VR. Bath-application of NMDA (2-25 mumol/l) increased amplitude of the electrotonic potentials, induced spice discharges in DR and VR, a tonic component of electrotonic potentials. Bath-application of 2-APV (20 mumol/l) depressed spontaneous and NMDA-induced activity. The neuronal network of isolated dorsal horn (after splitting of the spinal cord) retained ability to generate spontaneous activity in DR which was intensified after bath-application of NMDA. No rhythmic activity appeared in the ventral part of the cord. The location of NMDA-sensitive neuronal network generating rhythmic (motor) activity in the spinal cord is discussed.


Alternative splicing of amelogenin mRNA from rat incisor ameloblasts.
Amelogenin proteins are a major component of the developing enamel matrix, and are likely to have a key role in the control of enamel biomineralization. The heterogeneity of amelogenin is in part due to alternative splicing of the amelogenin RNA transcripts. Several patterns of alternative splicing have been described in mouse, bovine, porcine, and human enamel, with all alternatively spliced products having homologous 5' and 3' sequences within the coding regions. In these studies, we have used anchored PCR to identify alternatively spliced amelogenin cDNA sequences in the rat. We found amelogenin cDNAs that could be divided into two groups based on their 3' sequence. Group 1 cDNAs had a novel terminal sequence that has not been previously identified, while group 2 cDNAs were similar to those previously identified in other animal species. We identified a sequence, identical to the novel 3' amelogenin cDNA sequence, in rat genomic DNA downstream from the previously identified exon 7. The putative amelogenin proteins predicted for the two groups differed in their predicted isoelectric points, with the novel group 1 proteins having a more basic isoelectric point.


Methodological challenges in assessing children's mental health services utilization.
This paper describes the reliability and validity of the service assessment for children and adolescents (SACA) for use among Spanish-speaking respondents. The test-retest reliability of the instrument was assessed in a randomly selected clinical sample of 146 Puerto Rican children and adolescents aged 4-17. Both parents and children were administered the SACA twice by independent interviewers over an average 12-day follow-up period. The accuracy of parental and youth self-reports was assessed by comparing these reports to information obtained from medical records. The results showed that parents and children (aged 11-17) were able to report with fair to moderate reliability any last year use of mental health services, any outpatient mental health services, and school services. Residential and hospitalization services were reported by both informants with substantial test-retest reliability. Slight or no test-retest reliability was obtained for parent and child on the use of the specific type of mental health professionals, as well as parental reports of several treatment modalities. Substantial sensitivity of the SACA was obtained when comparing medical records to parental and child reports to lifetime use of any service and outpatient mental health service. Moderate sensitivity was obtained for last year use of mental health services for both parent and child informants.


Occupation and mortality related to alcohol, drugs and sexual habits.
To identify opportunities for targeted prevention, we explored differences in occupational mortality from diseases and injuries related to alcohol consumption, sexual habits and drug abuse. Using data on all deaths among men and women aged 16-74 years in England and Wales during 1991-2000, we derived age- and social class-standardized proportional mortality ratios (PMRs) by occupation for cause of death categories defined a priori as potentially related to alcohol consumption, sexual habits or drug abuse. The highest mortality from alcohol-related diseases and injuries was observed in publicans and bar staff (both sexes) and in male caterers, cooks and kitchen porters and seafarers. Male seafarers had significantly elevated PMRs for cirrhosis (179), 'other alcohol-related diseases' (275), cancers of the liver (155), oral cavity (275) and pharynx (267) and injury by fall on the stairs (187). PMRs for human immunodeficiency virus infection (HIV)/acquired immunodeficiency syndrome (AIDS) were particularly high in tailors and dressmakers (918, 95% CI: 369-1890, in men; 804, 95% CI: 219-2060, in women) and male hairdressers (918, 95% CI: 717-1160). Most jobs with high mortality from HIV/AIDS also had more deaths than expected from viral hepatitis. Of seven jobs with significantly high PMRs for both drug dependence and accidental poisoning by drugs, four were in the construction industry (male painters and decorators, bricklayers and masons, plasterers, and roofers and glaziers). Our findings highlight major differences between occupations in mortality from diseases and injuries caused by alcohol, sexual habits and drug abuse. Priorities for preventive action include alcohol-related disorders in male seafarers and drug abuse in construction workers.


Hybrid gait training with an overground robot for people with incomplete spinal cord injury: a pilot study.
Locomotor training has proved to provide beneficial effect in terms of mobility in incomplete paraplegic patients. Neuroprosthetic technology can contribute to increase the efficacy of a training paradigm in the promotion of a locomotor pattern. Robotic exoskeletons can be used to manage the unavoidable loss of performance of artificially driven muscles. Hybrid exoskeletons blend complementary robotic and neuro-prosthetic technologies. The aim of this pilot study was to determine the effects of hybrid gait training in three case studies with persons with incomplete spinal cord injury (iSCI) in terms of locomotion performance during assisted gait, patient-robot adaptations, impact on ambulation and assessment of lower limb muscle strength and spasticity. Participants with iSCI received interventions with a hybrid bilateral exoskeleton for 4 days. Assessment of gait function revealed that patients improved the 6 min and 10 m walking tests after the intervention, and further improvements were observed 1 week after the intervention. Muscle examination revealed improvements in knee and hip sagittal muscle balance scores and decreased score in ankle extensor balance. It is concluded that improvements in biomechanical function of the knee joint after the tested overground hybrid gait trainer are coherent with improvements in gait performance.


Incorporation of a phospholipid precursor into the hemochorionic and yolk sac placentas associated rat embryos.
Pregnant Long-Evans rats were subjected to a teratogenic regimen, i.e., were fed a synthetic diet lacking folic acid and containing 9-methylpteroylglutamic acid on the 11th to 14th days of gestation. Experimental and control pregnant rats injected with 10 muCi of [2-14C] ethanolamine on the 14th day were killed 1 or 2 days later. The total radioactivity and radioactivities of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and lysophosphatidylethanolamine (LPE) were determined in chloroform extracts of homogenates and subcellular fractions prepared from hemochorionic and yolk sac placentas and maternal liver. The distribution of radioisotope into PC and PE of control and experimental yolk sac placentas was similar, and paralleled the distribution in maternal liver. However, the distribution of radioisotope into PC and PE of the hemochorionic placentas did not parallel that of the maternal liver, and radiolabeled PC accumulated faster in experimental placentas than in controls. We suggest that the ability of the hemochorionic placenta to synthesize PC from PE was impaired by the teratogenic regimen, and that the organ took up relatively more PC from the maternal plasma. We propose that this teratogen-induced shift from placental lecithin synthesis to selective lecithin uptake underlies the previous finding of an increased accumulation of radio-labeled PC in embryos from pregnant females subjected to this teratogenic regimen (Chepenik and Waite, '73).


Quantifying carbon mitigation wedges in U.S. cities: near-term strategy analysis and critical review.
A case study of Denver, Colorado explores the roles of three social actors-individual users, infrastructure designer-operators, and policy actors-in near-term greenhouse gas (GHG) mitigation in U.S. cities. Energy efficiency, renewable energy, urban design, price- and behavioral-feedback strategies are evaluated across buildings-facilities, transportation, and materials/waste sectors in cities, comparing voluntary versus regulatory action configurations. GHG mitigation impact depends upon strategy effectiveness per unit, as well as societal participation rates in various action-configurations. Greatest impact occurs with regulations addressing the vast existing buildings stock in cities, followed by voluntary behavior change in electricity use/purchases, technology shifts (e.g., to teleconferencing), and green-energy purchases among individual users. A portfolio mix of voluntary and regulatory actions can yield a best-case maximum of ~1% GHG mitigation annually in buildings and transportation sectors, combined. Relying solely on voluntary actions reduces mitigation rates more than five-fold. A portfolio analysis of climate action plans in 55 U.S. cities reveals predominance of voluntary outreach programs that have low societal participation rates and hence low GHG impact, while innovative higher-impact behavioral, technological, and policy/regulatory strategies are under-utilized. Less than half the cities capitalize on cross-scale linkages with higher-impact state-scale policies. Interdisciplinary field research can help address the mis-match in plans, actions, and outcomes.


[From gene to disease; mutations in interleukin-12-receptor-beta 1- and interferon-gamma-receptor-1 lead to nontuberculous mycobacterial infections and salmonellosis].
In patients with severe and relapsing infections with non-tuberculous mycobacteria and Salmonella autosomal recessive as well as dominant-negative mutations are shown in genes for receptors of type-1 cytokines: the IL-12 receptor and the IFN-gamma receptor. In case of an impaired capacity to produce these cytokines or--given an abnormal receptor--to react to them, the cellular immune reaction does not run a normal course and the susceptibility to infection by intracellular pathogens is enhanced.


Physical, emotional and sexual adolescent abuse victimisation in South Africa: prevalence, incidence, perpetrators and locations.
Physical, emotional and sexual abuse of children is a major problem in South Africa, with severe negative outcomes for survivors. To date, no known studies have used data directly obtained from community-based samples of children to investigate prevalence, incidence, locations and perpetrators of child abuse victimisation. This study aims to investigate prevalence and incidence, perpetrators, and locations of child abuse victimisation in South Africa using a multicommunity sample. 3515 children aged 10-17 years (56.6% female) were interviewed from all households in randomly selected census enumeration areas in two South African provinces. Child self-report questionnaires were completed at baseline and at 1-year follow-up (96.7% retention). Prevalence was 56.3% for lifetime physical abuse (18.2% past-year incidence), 35.5% for lifetime emotional abuse (12.1% incidence) and 9% for lifetime sexual abuse (5.3% incidence). 68.9% of children reported any type of lifetime victimisation and 27.1% reported lifetime multiple abuse victimisation. Main perpetrators of abuse were reported: for physical abuse, primary caregivers and teachers; for emotional abuse, primary caregivers and relatives; and for sexual abuse, girlfriend/boyfriends or other peers. This is the first study assessing current self-reported child abuse through a large, community-based sample in South Africa. Findings of high rates of physical, emotional and sexual abuse demonstrate the need for targeted and effective interventions to prevent incidence and re-victimisation.


Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders.
The goal here is to describe our current understanding of heme metabolism and the deleterious effects of "free" heme on immunological processes, endothelial function, systemic inflammation, and various end-organ tissues (e.g., kidney, lung, liver, etc.), with particular attention paid to the role of hemopexin (HPX). Because heme toxicity is the impetus for much of the pathology in sepsis, sickle cell disease (SCD), and other hemolytic conditions, the biological importance and clinical relevance of HPX, the predominant heme binding protein, is reinforced. A perspective on the function of HPX and haptoglobin (Hp) is presented, updating how these two proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail hemolysis and/or systemic intravascular (IVH) inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of hemolysis, such as SCD, sepsis, hemolytic-uremic syndrome, and conditions involving IVH and extravascular hemolysis (EVH), such as that generated by extracorporeal circulation during cardiopulmonary bypass (CPB) and from blood transfusions. We propose that quantitating the amounts of plasma heme, HPX, Hb-Hp, heme-HPX, and heme-albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted plasma protein supplementation (i.e., "replenishment") therapies for patients with heme toxicity due to HPX depletion.


Hepatobiliary abnormalities of AIDS.
Liver disease, although usually asymptomatic, is a frequent accompaniment of AIDS. Hepatomegaly and macrosteatosis are prevalent but non-specific findings. Evidence of remote hepatitis B virus infection is extremely common; however, the HBsAg carrier state, chronic active hepatitis, or cirrhosis occur no more frequently in AIDS patients than in the general population. Opportunistic intrahepatic infections (such as MAI, fungi, and CMV) or neoplasms (such as lymphoma or KS) usually reflect a disseminated process; liver involvement generally does not directly cause morbidity or result in death. Although biochemical liver tests are commonly elevated in the AIDS population, alkaline phosphatase has proved to be the most specific enzyme for infiltrative processes. Percutaneous liver biopsy has a high diagnostic yield, although the treatment options are currently limited. Acalculous cholecystitis and biliary tract obstruction have been recently described and probably result from CMV and/or cryptosporidial infection. Radiologic features of papillary stenosis and/or sclerosing cholangitis have been demonstrated. In contrast to hepatic parenchymal disease, these entities may be amenable to surgical or endoscopic therapeutic maneuvers.


Bisphenol A Electrochemical Sensor Using Graphene Oxide and β-Cyclodextrin-Functionalized Multi-Walled Carbon Nanotubes.
Bisphenol A, an endocrine disrupting compound, is widely used in food and beverage packaging, and it then leaches in food and source water cycles, and thus must be monitored. Here, we report a simple, low-cost and sensitive electrochemical sensor using graphene oxide and β-cyclodextrin functionalized multiwalled carbon nanotubes for the detection of BPA in water. This sensor electrode system combines the high surface area of graphene oxide and carbon nanotubes, and the superior host-guest interaction capability of β-cyclodextrin. A diffusion-controlled oxidation reaction involving equal numbers of protons and electrons facilitated the electrochemical sensing of BPA. The sensor showed a two-step linear response from 0.05 to 5 μM and 5-30 μM with a limit of detection of 6 nM. The sensors also exhibited a reproducible and stable response over one month with negligible interference from common inorganic and organic species, and an excellent recovery with real water samples. The proposed electrochemical sensor can be promising for the development of simple low-cost water quality monitoring system for monitoring of BPA in water.


Health Service Access Among Homeless Veterans: Health Access Challenges Faced by Homeless African American Veterans.
Veteran homelessness is a public health crisis, especially among the disproportionate number of minority veterans in the homeless veteran population. African American homeless veterans in particular face unique challenges accessing appropriate health care services to meet their medical needs. Their needs are often underrepresented in the literature on veteran homelessness. Drawing together over 80 studies and government reports from the last two decades, this review provides a timely synopsis of homeless veterans' health care access, with a particular focus on the barriers faced by African American veterans. This review employs Penchansky and Thomas' Access Model to frame health access barriers faced by homeless veterans, dialing in on what is known about the experience of African American veterans, within the five dimensions of access: Availability, Accessibility, Accommodation, Affordability, and Acceptability. Actionable guidance and targeted interventions to address health access barriers for all veterans are delineated with a focus on the need to gather further data for African American homeless veterans and to consider tailoring interventions for this important and underserved group.


[Type I collagen in rat skin in an excess of dietary amino acids].
Type I collagen in skin of rats who were given redundant amounts of leucin, valine, methionine or phenyl alanine differed essentially from the normal level in the amino acidic composition. Considerable shifts in the value of pI of the proteins under study as compared with the normal level are found during isofocusing. When studying subunits of collagen preparations by the reverse-phase chromatography certain differences typical of each studied state are revealed in the elution profiles in normalcy and under amino acid loadings.


Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced activation in human monocyte-derived dendritic cells.
Dendritic cells (DCs) are key players in initiating and directing the immune response. Therefore, their activation state and functional differentiation need to be tightly controlled. The activating stimuli and their signaling networks have long been an area of focus in DC research. Recent investigations have also shed light on the mechanisms of counterregulation and fine-tuning of DC functions. One class of proteins involved in these processes is the family of suppressors of cytokine signaling (SOCS), whose members were originally described as feedback inhibitors of cytokine-induced JAK/STAT signaling. Essential roles in DC function have been assigned to SOCS1 and SOCS3. In this article, we show that SOCS2 also is involved in DC regulation. In human and in murine DCs, SOCS2 is a highly TLR-responsive gene, which is expressed in a time-delayed fashion beginning 8 h after TLR ligation. Functionally, silencing of SOCS2 in DCs results in hyperphosphorylation of STAT3 at later time points. As a consequence, SOCS2-deficient DCs secrete increased amounts of the cytokines IL-1β and IL-10, both being transcriptional targets of STAT3. We propose a model in which SOCS2 acts as a negative regulator of TLR-induced DC activation. The delayed expression of SOCS2 provides a mechanism of late-phase counterregulation and limitation of inflammation-driving DC activity.


Differential responsiveness of humans with early-stage schistosomiasis haematobium to Schistosoma haematobium soluble adult-worm and egg antigens.
Schoolchildren (7-8 years old) infected with Schistosoma haematobium were tested for lymphocyte proliferative responses, in vitro granuloma formation (IVGF), and cytokine release in T-cell Western assays and for serum antibody reactivity by enzyme-linked immunosorbent assay (ELISA) and immunoblotting against S. haematobium soluble adult-worm (SAWA) and egg (SEA) antigens. The lymphoproliferative response rate of individual subjects against 10 SAWA and 15 SEA electroseparated bands ranged from 0 to 33% and from 11 to 66%, respectively. The SAWA bands essentially failed to elicit significant IVGF, in contrast to the SEA bands, all of which were capable of inducing IVGF from peripheral blood mononuclear cells (PBMC) of 30-80% of individual donors. The exclusive ability of SEA bands to induce IVGF could not be attributed to selective release of interleukin 2 (IL-2), IL-4, or interferon-gamma, as SEA and SAWA bands were capable of eliciting release of a similar array of cytokines in supernatants of 4-day PBMC cultures. The antibody response to SEA was stronger than that to SAWA, yet the proportion of SAWA bands binding humoral antibodies of individual donors was significantly larger than that observed for SEA. The study thus suggests that humans with early-stage S. haematobium infection respond poorly to SAWA but mount strong cellular immune responses to SEA that result in granuloma and antibody formation.


Activation of the GP130-STAT3 axis and its potential implications in nonalcoholic fatty liver disease.
The status of the GP130-STAT3 signaling pathway in humans with nonalcoholic fatty liver disease (NAFLD) and its relevance to disease pathogenesis are unknown. The expression of the gp130-STAT3 axis and gp130 cytokine receptors were studied in subjects with varying phenotypes of NAFLD including nonalcoholic steatohepatitis (NASH) and compared with lean and weight-matched controls without NAFLD. Gp130 and its downstream signaling element (Tyk2 and STAT3) expression were inhibited in obese controls whereas they were increased in NAFLD. IL-6 levels were increased in NASH and correlated with gp130 expression (P < 0.01). Palmitate inhibited gp130-STAT3 expression and signaling. IL-6 and palmitate inhibited hepatic insulin signaling via STAT3-dependent and independent mechanisms, respectively. STAT3 overexpression reversed palmitate-induced lipotoxicity by increasing autophagy (ATG7) and decreasing endoplasmic reticulum stress. These data demonstrate that the STAT3 pathway is activated in NAFLD and can worsen insulin resistance while protecting against other lipotoxic mechanisms of disease pathogenesis.


Somatotypes of Nigerian athletes of several sports.
Somatotype ratings and percentage body fat of 131 elite Nigerian male athletes, average 24.2 years of age, and belonging to badminton (n = 18), basketball (n = 30), field hockey (n = 24), handball (n = 16), judo (n = 18), and soccer (n = 25) teams were determined. Basketball, handball and soccer players were taller and heavier, and had low percent fat values as compared with the other athletic groups. Judokas and hockey players were endomesomorphs. Other sports groups were predominantly ectomesomorphs.


Maximizing influenza vaccination uptake among healthcare personnel in Israel: lessons learned from mandatory vaccination policy in the United States.
Maximizing vaccination uptake is crucial in generating herd immunity and preventing infection incidence (Quach et al., Am J Infect Control 11:1017-23, 2013). Vaccination of healthcare personnel (HCP) against influenza is vital to influenza infection control in healthcare settings, given the consistent exposure of HCP to high-risk patients like: those with compromised immune systems, children, and the elderly (Johnson & Talbot, Curr Opin Infect Dis 24: 363-369, 2011). Influenza vaccination uptake among HCP remains suboptimal: in 2017-18, 47.6% of HCP who worked in settings where influenza vaccination was not mandatory were vaccinated against influenza in United States (Black et al., Morb Mortal Wkly Rep 67: 1050, 2018). Mandatory vaccination policies result in HCP influenza vaccination uptake rates substantially higher than opt-in influenza vaccination campaigns (94.8% vs. 47.6%) (Black et al., Morb Mortal Wkly Rep 67: 1050, 2018). The Israel Journal of Health Policy Research has published articles focused on the issues of influenza vaccination (Yamin et al., Isr J Health Policy Res 3: 13, 2014), improving influenza vaccination coverage of HCP (Weber et al., Isr J Health Policy Res 5: 1-5, 2016), influenza vaccination motivators among HCP (Nutman and Yoeli, Isr J Health Policy Res 5: 52, 2016), legal imposition of vaccination (Kamin-Friedman, Isr J Health Policy Res 6:58, 2017), and mandatory vaccination (Gostin, Cell Biosci 8: 1-4, 2018). Each article explores factors influencing disease prevention from different angles within an Israeli context. This article attempts to fuse these topics by investigating how to apply aspects of American mandatory influenza vaccination policy targeted at HCP in an Israeli context. Critical document analysis was conducted on relevant literature and policy discussing influenza prevention interventions among HCP within the United States. Mandatory vaccination policies were highlighted. A discussion of the professional responsibility of HCP to vaccinate against influenza serves as background. Case studies of hospitals in the United States that implemented mandatory vaccination policies for their employees are analyzed. The article concludes with analysis exploring how qualities of mandatory influenza vaccination policy of HCP could take shape in Israel, giving contextual limitations, urging Israeli health policy makers to reflect on lessons learned from the American case study. Mandatory HCP influenza vaccination policies in comparison to non-mandatory interventions are most effective in obtaining maximum influenza vaccination uptake among HCP (Black et al., Morb Mortal Wkly Rep 67: 1050, 2018). Many HCP cite individual objections to influenza vaccination rooted in personal doubts and ethical concerns. The ethical responsibility of HCP to their patients and work environments to prevent and lower influenza infection incidence arguably overrules such individual objections. Mandatory HCP influenza vaccination policies are an effective method of maximizing HCP influenza vaccine uptake and minimizing the spread of the influenza virus within healthcare settings. Still, cultural, social and political sensitivity must be taken into consideration when implementing both full-on mandatory HCP influenza vaccination policies and/or aspects of mandatory policies, especially within an Israeli context.


The efficiency of endothelin receptor antagonist bosentan for pulmonary arterial hypertension associated with congenital heart disease: A systematic review and meta-analysis.
Oral bosentan has been widely applied in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A systemic review and meta-analysis was conducted for a therapeutic evaluation of oral bosentan in both adult and pediatric patients with PAH-CHD. The acute responses and a long-term effect were respectively assessed in a comparison with baseline characteristics, and the improvement of exercise tolerance was analyzed. PubMed, Medline, Embase, and Cochrane Central Register of clinical controlled trails or observational studies have been searched for a recording of bosentan effects on the PAH-CHD participants. For mortality and rate of adverse events (AEs), it was described in detail. Randomized-effects model or fixed-effects model was used to calculate different effective values with a sensitivity analysis. Seventeen studies were pooled in this review, and 3 studies enrolled the pediatric patients. Among all studies, 456 patients were diagnosed with PAH-CHD, and 91.7% were treated with oral bosentan. With a term less than 6 months of bosentan therapy, there existed a significant improvement in 6-minute walk distance (6MWD) and the World Health Organization functional class (WHO-FC), but no such differences in Borg dyspnea index scores (BDIs) and the resting oxygen saturation (SpO2). Although with a prolonged treatment, not only 6MWD and FC, but also the resting SpO2 and heart rate were changed for a better exercise capability. Additionally, compared with the basic cardiopulmonary hemodynamics, it showed a statistically significant difference in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRi). Although a limitation of pooled studies with comparative outcomes of different terms, outcomes presented a lower WHO-FC which contributes to a success in a prolonged treatment. Bosentan in PAH-CHD is well established and still requires clinical trials for an identification of its efficiency on CHD patients for an optimized period lessening a serious complication and the common AEs.


Wogonin induces cell cycle arrest and erythroid differentiation in imatinib-resistant K562 cells and primary CML cells.
Wogonin, a flavonoid derived from Scutellaria baicalensis Georgi, has been demonstrated to be highly effective in treating hematologic malignancies. In this study, we investigated the anticancer effects of wogonin on K562 cells, K562 imatinib-resistant cells, and primary patient-derived CML cells. Wogonin up-regulated transcription factor GATA-1 and enhanced binding between GATA-1 and FOG-1, thereby increasing expression of erythroid-differentiation genes. Wogonin also up-regulated the expression of p21 and induced cell cycle arrest. Studies employing benzidine staining and analyses of cell surface markers glycophorin A (GPA) and CD71 indicated that wogonin promoted differentiation of K562, imatinib-resistant K562, and primary patient-derived CML cells. Wogonin also enhanced binding between GATA-1 and MEK, resulting in inhibition of the growth of CML cells. Additionally, in vivo studies showed that wogonin decreased the number of CML cells and prolonged survival of NOD/SCID mice injected with K562 and imatinib-resistant K562 cells. These data suggested that wogonin induces cycle arrest and erythroid differentiation in vitro and inhibits proliferation in vivo.


[Adaptation and ecological resistance].
The notion fitness, widely used in genetics usually serves to measure a relative rate of organism reproduction. Another important character of an organism is its ecological resistance which is basically the product of macroevolution. It can be determined as a probability of an organism survival and participation in reproduction of the species. Ecological resistance determines the level of the accidental death of organisms that are genetically valuable. For the comparison of ecological resistance in different organisms and species the negative meanings of the Malthusian parameter can be used. Ecological resistance depends on the presence in genomes of essential genes and fairly complete sets of nonessential, or adaptive, genes which can reside in genomes both as "plus" and "minus" alleles. The recovery of complete sets of adaptive genes lost as a result of mutations and, thus, of a high level of ecological resistance in organisms is provided by genetic exchange between them. With respect to mutations leading to the increase in fitness the effect of genetic exchange is negative since it leads to the formation of recombination load, i.e. a decrease in fitness of the offspring. In microevolutionary processes, the elevation in ecological resistance level does not take place since it requires a long time for the formation of new genes and new elements of organization in the process of positive selection. At the same time, a constant recovery of a high level of ecological resistance of the species decreased as a result of mutations takes place in some individuals due to genetic exchange. Mutations affecting ecological resistance of an organism, as a rule, cause a decrease in its viability and they are usually excluded from populations as a result of negative (stabilizing) selection.


Synaptic organization and ionic basis of on and off channels in mudpuppy retina. I. Intracellular analysis of chloride-sensitive electrogenic properties of receptors, horizontal cells, bipolar cells, and amacrine cells.
Intracellular recordings from receptors, horizontal cells, bipolars, and amacrines have been carried out in the perfused mudpuppy eyecup. The introduction of a chloride-free (c-f) medium results in initial transient potential changes in many cells followed by a slow loss of light-evoked activity of the depolarizing bipolar, the horizontal cell, and the on depolarization of amacrine cells. The hyperpolarizing bipolar remains responsive to light stimulation in a c-f medium, but the antagonistic surround mechanism is abolished. These effects are reversible after returning to a normal ionic medium. The results of this study provide insight into the retinal connections which underlie ganglion cell receptive field organization. It is concluded that the depolarizing bipolar is excitatory to on ganglion cells and is also the pathway for on-excitation of on-off cells. The hyperpolarizing bipolar mediates the off discharge of off and on-off cells. Amacrine cells receive input from both depolarizing and hyperpolarizing bipolar cells. These findings raise the possibility that transmembrane movements of chloride ions are critical for the light responsiveness of horizontal and depolarizing bipolar cell activity.


Assessing sickness behavior in the French: Validation of the French translation of the sickness questionnaire (SicknessQ) in a non-clinical French population.
The Sickness Questionnaire (SicknessQ) is a questionnaire developed to assess symptoms of sickness behavior, including somatic, behavioral, and affective dimensions. To promote cross-cultural assessments of sickness behavior, we aim to expand the use of this questionnaire to other populations and languages. The aim of the present study was to evaluate the French translation of SicknessQ in a French-speaking general population during the COVID-19 pandemic. One hundred and thirty-nine individuals completed the SicknessQ online, along with the construct criteria measures of self-rated health, state anxiety (STAI-S), and depressive symptoms (PHQ-9). The principal component analyses revealed two components: the first component included seven items concerning mood, motivation and experiences of fatigue and pain; the second component included three items concerning somatic sickness symptoms. Higher scores on the total scale and the two component subscales were associated with poorer self-rated health and higher STAI-S and PHQ-9 scores. Since the associations with construct criteria variables were relatively similar between the single- and the two-dimensional solutions, both the total scale and the subscales of the two components of the French SicknessQ can be used in future studies to measure sickness behavior in French-speaking populations.


Evaluation of a truncated recombinant flagellin subunit vaccine against Campylobacter jejuni.
A recombinant protein comprising the maltose-binding protein (MBP) of Escherichia coli fused to amino acids 5 to 337 of the FlaA flagellin of Campylobacter coli VC167 was evaluated for immunogenicity and protective efficacy against challenge by a heterologous strain of campylobacter, Campylobacter jejuni 81-176, in two murine models. The sequence of the flaA gene of strain 81-176 revealed a predicted protein which was 98.1% similar to that of VC167 FlaA over the region expressed in the fusion protein. Mice were immunized intranasally with two doses of 3 to 50 microgram of MBP-FlaA, given 8 days apart, with or without 5 microgram of the mutant E. coli heat-labile enterotoxin (LT(R192G)) as a mucosal adjuvant. The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum immunoglobulin G (IgG) responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA (>/=25 microgram) or coadministration of lower doses with the adjuvant. When vaccinated mice were challenged intranasally 26 days after immunization, the best protection was seen in animals given 50 microgram of MBP-FlaA plus LT(R192G). The protective efficacies of this dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 microgram of MBP-FlaA plus LT(R192G) intranasally were challenged orally with 8 x 10(10), 8 x 10(9), or 8 x 10(8) cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively.


Coagulase-negative staphylococcal endocarditis. Occurrence in patients with mitral valve prolapse.
Although coagulase-negative staphylococci (CoNS) are frequent etiologic agents in prosthetic valve endocarditis, they rarely infect native heart valves. We report three cases of CoNS endocarditis in patients with mitral valve prolapse (MVP). Review of other reports of MVP-associated endocarditis and of the limited experience with CoNS infection of native heart valves suggests that our experience is not unique. Coagulase-negative staphylococcal endocarditis superimposed on MVP may be difficult to recognize and to treat. The cardiac dysfunction can be quite subtle, the clinical course indolent, the blood culture results difficult to interpret, and the response to antimicrobial agents suboptimal.


Inhibitory effect of ethyl acetate extract of the shaggy inc cap medicinal mushroom, Coprinus comatus (Higher Basidiomycetes) fruit bodies on cell growth of human ovarian cancer.
In a previous study, we screened organic extracts of different mushroom mycelia and picked ethyl acetate extract of Coprinus comatus as one of the most active extracts against human ovarian cancer cells. In the current study, we extracted a dry powder of C. comatus fruit bodies using ethyl acetate and examined its effect on the viability of three cell lines originated from human ovarian cancer (ES-2, SKOV-3, and SW-626). This extract was active against all tested cell lines, in a dose-dependent manner (concentrations 50-200 µg/mL, P<0.01). In an attempt to segregate the active fraction, we subjected the extract to chromatography on a silica gel column. The effect of six different fractions and of the crude extract on the viability of ES-2 cells was examined after exposure time of 24 h. Fraction F (last eluted) was significantly more effective than crude extract in the reduction of cell viability (P<0.01). Fraction F was also significantly more active than crude extract in the reduction of viability of SKOV-3 cells. We next identified some of the compounds of fraction F (mainly fatty acids) by gas chromatography-mass spectrometry. In summary, ethyl acetate extract of C. comatus reduced viability of three lines of human ovarian cancer. Fractionation of this extract by a silica gel column enabled the selection of a fraction significantly more active than the original extract.


[Clinical aspects of disseminated nonspecific pneumonia].
Characteristic features of the clinicoroentgenological picture of extended nonspecific pneumonia are described. The frequency of difficulties with the differential diagnosis and the sources of the diagnostic mistakes (exceeding 70 per cent by the materials of the authors) are analyzed. The basic diagnostic criteria are indicated and the possibilities for test therapy and computer diagnosis are defined. This will decrease the periods for the disease diagnosis.


Middle-age male mice have increased severity of experimental autoimmune encephalomyelitis and are unresponsive to testosterone therapy.
Treatment with sex hormones is known to protect against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, little is known about how age affects the course of EAE or response to hormone treatment. This study demonstrates striking differences between middle-age vs young C57BL/6 male mice in the clinical course of EAE and response to both testosterone (T4) and estrogen (E2) hormone therapy. Unlike young males that developed an acute phase of EAE followed by a partial remission, middle-age males suffered severe chronic and unremitting EAE that was likely influenced by alterations in the distribution and function of splenic immunocytes and a significant reduction in suppressive activity of CD4+CD25+ regulatory T cells in the spleen and spinal cord. Middle-age males had reduced numbers of splenic CD4+ T cells that were generally hypoproliferative, but enhanced numbers of splenic macrophages and MHC class II-expressing cells, and increased secretion of the proinflammatory factors IFN-gamma and MCP-1. Surprisingly, middle-age males were unresponsive to the EAE-protective effects of T4 and had only a transient benefit from E2 treatment; young males were almost completely protected by both hormone treatments. T4 treatment of young males inhibited proliferation of myelin oligodendrocyte glycoprotein 35-55-specific T cells and secretion of TNF-alpha and IFN-gamma. The effects of T4 in vivo and in vitro were reversed by the androgen receptor antagonist, flutamide, indicating that the regulatory effects of T4 were mediated through the androgen receptor. These data are the first to define age-dependent differences in EAE expression and response to hormone therapy.


Role of endothelin in diabetic retinopathy.
Endothelin-1 (ET-1) is a 21 amino acid peptide originally purified from conditioned medium of cultures of porcine aortic endothelial cells. It is now known that there are three endothelin genes in the human genome (ET-1, ET-2, and ET-3 genes). ET-1 and ET-2 are both strong vasoconstrictors, whereas ET-3 is a potentially weaker vasoconstrictor compared to the other two isoforms. Besides being a very potent vasoconstrictor, ET-1 also acts as a mitogen on the vascular smooth muscle and thus it may play a role in the development of vascular diseases. There is evidence that impaired auto-regulation of blood flow is involved in the pathogenesis of diabetic microangiopathy. It is known that the ability of the diabetic's circulation to distribute blood is affected, especially during increased blood flow. In most tissues this causes no serious burden, but three tissues are usually susceptible to disturbance. They are the retina, renal cortex, and peripheral nerves. Retinal vascular auto-regulation is defined as the ability of the blood vessels to keep blood flow constant under varying perfusion pressure in order to match it to tissue oxygen and metabolic requirements. The failure of auto-regulation is an important and often early feature of diabetic retinopathy. Since human retina vessels lack extrinsic innervation, retinal vessel calibre and local blood flow are normally regulated by non-nervous mechanisms intrinsic to the retina. There is now a considerable body of evidence suggesting that retinal pericytes are the main regulators of vascular tone in the retinal capillaries because they contain components of contractile proteins similar to vascular smooth muscle cells and because they also possess ET-1 receptors. Furthermore. ET-1 has been shown to cause vasoconstriction of retinal vessels as well as to have mitogenic effects on retinal pericytes. Hence, alterations in the pericyte-ET interaction may have a role causing early hemodynamic and histopathological abnormalities found in diabetic retinopathy. On the contrary, Chakrabarti et al. demonstrate that retinas from the chronic diabetic BB/W rats (6 months) show an increase in ET-1, ET-3, ET(A) receptor and ET(B) receptor mRNA expressions when compared to those from control rats. Similar results are noted by them using immunohistochemical methods. Finally, an increased ocular, and retina tissue levels of ET-1 in diabetic rats have also been reported by Chakravarthy et al., as well as by Takagi et al. All of these findings suggest that endothelins may also be involved in the pathogenesis of more advanced diabetic retinopathy, such as capillary occlusion and subsequent neovascularization. This review summarizes the reported literature on the role of ET-1 in the development of diabetic retinopathy.


Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays.
Microfluidic flow assays (MFA) that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s⁻¹ through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (Lag(T)), the rate of platelet accumulation (V(PLT)), and platelet surface coverage (SC). A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF) levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to V(PLT) and SC at all wall shear rates. A longer Lag(T) for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s⁻¹ and 300 s⁻¹. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI) resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104) and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay.


Formation of ultralong DH regions through genomic rearrangement.
Cow antibodies are very unusual in having exceptionally long CDR H3 regions. The genetic basis for this length largely derives from long heavy chain diversity (DH) regions, with a single "ultralong" DH, IGHD8-2, encoding over 50 amino acids. Many bovine IGHD regions have sequence similarity but have several nucleotide repeating units that diversify their lengths. Genomically, most DH regions exist in three clusters that appear to have formed from DNA duplication events. However, the relationship between the genomic arrangement and long CDR lengths is unclear. The DH cluster containing IGHD8-2 underwent a rearrangement and deletion event in relation to the other clusters in the region corresponding to IGHD8-2, with possible fusion of two DH regions and expansion of short repeats to form the ultralong IGHD8-2 gene. Length heterogeneity within DH regions is a unique evolutionary genomic mechanism to create immune diversity, including formation of ultralong CDR H3 regions.


Doppler waveform analysis in the management of lower limb arterial disease.
Arterial disease changes the shape of Doppler ultrasound waveforms recorded noninvasively from arteries in the lower limbs. These changes can be described numerically by computer analysis of waveforms, and techniques currently in use are pulsatility index, Laplace transform and principal component analysis. These waveform analysis methods allow assessment of aortoiliac disease from Doppler recordings at the femoral artery. In addition, the femorodistal segment can be evaluated by comparing femoral and distal waveforms, even in the presence of more proximal arterial disease. Other possible applications for waveform analysis include noninvasive follow-up of angioplasty or bypass grafts and the detection of early, presymptomatic arterial disease. Experience in recording Doppler waveforms is important if variability is to be minimised. Currently, these methods allow exclusion of aortoiliac disease prior to femorodistal grafting but their other potential roles require further clinical evaluation.


Pleiotropic effects of adaptation to a single carbon source for growth on alternative substrates
It is frequently assumed that populations of genetically modified microorganisms will perform their intended function and then disappear from the environment due to inherent fitness disadvantages resulting from their genetic alteration. However, modified organisms used in bioremediation can be expected to adapt evolutionarily to growth on the anthropogenic substrate that they are intended to degrade. If such adaptation results in improved competitiveness for alternative, naturally occurring substrates, then this will increase the likelihood that the modified organisms will persist in the environment. In this study, bacteria capable of degrading the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) were used to test the effects of evolutionary adaptation to one substrate on fitness during growth on an alternative substrate. Twenty lineages of bacteria were allowed to evolve under abundant resource conditions on either 2,4-D or succinate as their sole carbon source. The competitiveness of each evolved line was then measured relative to that of its ancestor for growth on both substrates. Only three derived lines showed a clear drop in fitness on the alternative substrate after demonstrable adaptation to their selective substrate, while five derived lines showed significant simultaneous increases in fitness on both their selective and alternative substrates. These data demonstrate that adaptation to an anthropogenic substrate can pleiotropically increase competitiveness for an alternative natural substrate and therefore increase the likelihood that a genetically modified organism will persist in the environment.


The effect of sonophoresis on topical anesthesia: a pilot project.
The dental anesthesia sonophoresis device (DASD) is a novel device that is intended to reduce the discomfort associated with intraoral mucosa needle puncture. The DASD produces ultrasonic energy that provides a sonophoretic effect on the oral mucosa, generating microchannels through the lipids between the keratinized cells that make up the stratum corneum. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings and reducing the perception of pain caused by needle penetration. The aim of this study is to evaluate whether topical anesthesia applied using the DASD will reduce the discomfort of the needle puncture when compared to the control device. A split-mouth model, using 50 healthy subjects with puncture site at the maxillary canine vestibule, was used for this study. Subjects received a needle puncture on both sides of the mouth. Prior to the needle puncture, there was randomized application of 5% lidocaine with the DASD and a control device. Subjects rated their discomfort after needle punctures utilizing the visual analog scale pain scoring system. There was no statistically significant difference in the pain perception using the DASD versus the control device.


Where is mineral ballast important for surface export of particulate organic carbon in the ocean?
Correlations between particulate organic carbon (POC) and mineral fluxes in the deep ocean have inspired the inclusion of "ballast effect" parameterizations in carbon cycle models. A recent study demonstrated regional variability in the effect of ballast minerals on the flux of POC in the deep ocean. We have undertaken a similar analysis of shallow export data from the Arctic, Atlantic, and Southern Oceans. Mineral ballasting is of greatest importance in the high-latitude North Atlantic, where 60% of the POC flux is associated with ballast minerals. This fraction drops to around 40% in the Southern Ocean. The remainder of the export flux is not associated with minerals, and this unballasted fraction thus often dominates the export flux. The proportion of mineral-associated POC flux often scales with regional variation in export efficiency (the proportion of primary production that is exported). However, local discrepancies suggest that regional differences in ecology also impact the magnitude of surface export. We propose that POC export will not respond equally across all high-latitude regions to possible future changes in ballast availability.